Differential response of normal and cirrhotic liver to vasoactive agents. A study in the isolated perfused rat liver

Abstract

In cirrhosis, endogenous vasoactive agents could act as modulators of intrahepatic resistance and thus portal pressure. The aim of this work was to study the effects of norepinephrine, angiotensin II and arg8-vasopressin on intrahepatic portal resistance in isolated perfused livers from normal rats and rats with carbon tetrachloride-induced cirrhosis. Livers were perfused at a constant pressure and the measured variable was portal blood flow. Dose-response curves were obtained by cumulative addition of agonists to the perfusate. The three vasoactive agents increased resistance in normal and cirrhotic livers. The maximal amplitude of response was similar in normal and cirrhotic livers. The cirrhotic livers exhibited an increased sensitivity to norepinephrine, a decreased sensitivity to angiotensin II but an unchanged sensitivity to arg8-vasopressin. The shape of the dose-response curve for norepinephrine and arg8-vasopressin, but not for angiotensin II, was modified in cirrhotic livers. We conclude that the cirrhotic liver retains a strong vascular reactivity to vasoactive agents and particularly to norepinephrine.